The cyclic phosphonic acid sodium salt (a sodium salt of 9-octadecenoic acid(9Z)-(2-hydroxy-2-oxo-2λ5-1,2-oxaphosphoran-4-yl)methyl ester) represented by the following formula (1) is a compound, typically referred to as 2ccPA.

2ccPA is known to have a potent analgesic action (Patent Literature 1) and is also expected to serve as an anti-cancer agent because of its infiltration-inhibitory activity on cancer cells (Patent Literature 2), an osteoarthritis therapeutic agent because of its accelerated production of hyaluronic acid (Patent Literature 3), or other agents.
2ccPA has traditionally been produced by the production method shown in the following reaction scheme-1 (Patent Literature 2 and 4 and Non-patent Literature 1 and 2).

Specifically, iodine compound (5a), which is obtained by the production method disclosed in Non-patent Literature 2, is first reacted with trimethyl phosphite to prepare dimethyl phosphonate (6a). Subsequently, p-toluenesulfonic acid (p-TsOH) is allowed to act on compound (6a) to obtain compound (8a). After oleic acid is introduced to compound (8a) to prepare compound (9a), demethylation is performed, and further a sodium salt is formed, thereby producing 2ccPA.
However, because of the absence of optimization of the reaction conditions for each step and the need for purification by silica gel column chromatography in each step, the total yield of 2ccPA in this production method, obtained by performing the 5 steps described above, is as low as 18.7%, when calculated from the yields disclosed in the literature. This indicates that the method is not suitable for synthesis on a large scale. In addition, the use of bromotrimethylsilane (TMSBr) in the demethylation step generates hydrogen bromide as a by-product, which makes the reaction system strongly acidic, making the product prone to decomposition. In actuality, the yield in the demethylation step is as low as 38%.
In the final step, compound (10a) is formed into a sodium salt using a sodium hydroxide aqueous solution to induce 2ccPA. However, because freeze-drying is performed without purification, strongly basic sodium hydroxide may come to be mixed with the solid of 2ccPA. Thus, decomposition of 2ccPA by sodium hydroxide is unavoidable, causing a storage stability problem.
Therefore, there has been a demand for the development of a method for producing a crystal of 2ccPA that is convenient, and that produces a high-purity crystal exhibiting excellent storage stability at a high yield, as compared with the traditional known method.